1. Field of the Invention
The invention relates to the separation, detection and counting of single molecules at nanometer scale. More particularly, molecular separation is achieved by driving single molecules through a microfluidic or nanofluidic medium using programmable and coordinated electric fields, and detecting the molecules using nanoelectrode-gated tunneling methods, dielectric monitoring and other methods.
2. Background Information
A key step in the invention is the ability to fabricate a required nanometer-scale gap that is defined as the distance between a pair of sharp nanoelectrode tips. Such a gap is used in the present invention as a molecular detection gate. The following is a description of our recent invention, now U.S. Pat. No. 6,447,663, issued Sep. 10, 2002, for accomplishing the construction of such a nanogap.
Nanometer-scale modification of nanostructures can be carried out in liquids at ambient temperature and neutral pH through electric field-directed, programmable, pulsed electrolytic metal deposition or depletion. The use of pulsed current is a critical feature in the method, while temperature and pH are not critical parameters.
A programmable and short (time scale of nanoseconds to milliseconds) pulsed direct current source is used to control the number of atoms being deposited by the electrolytic metal reduction and deposition process. As shown in the following platinum deposition reaction at a cathode using water-soluble hexachloroplatinate, the number of electrons supplied can control the formation of metallic platinum. In electrolytic deposition, electric current and the duration of the current can control the number of electrons.[PtCl6]−2+4e−→Pt↓+6Cl−
Other water-soluble metal compounds that have been shown to be applicable include, but are not limited to, the following: PtCl4, OsCl3, Na2[PtCl6], Na2[OsCl6], (NH4)2RuCl6, K3RuCl6, Na2PdCl6, Na2IrCl6, (NH4)3IrCl6, (NH4)3RhCl6, K2PdCl4, (NH4)2PdCl4, Pd(NH3)4Cl2, ReCl3, NiCl2, CoCl2, PtO2, PtCl2, Pt(NH3)4Cl2, CuSO4, (NH4)6Mo7O24, NaAuCl4, K2[PtCl4], and K3Fe(CN)6. Combinations of two or more water-soluble metal compounds can be used sequentially or simultaneously.
As illustrated in FIG. 1, an embodiment of our recent invention involves a special utilization of a programmable current source 18 that can precisely control the number of electrons used to achieve the desired nanometer-scale electrolytic metal deposition. A nonconductive substrate 10 supports nanometer-sized electrodes in the form of a cathode 12 and anode 14 (also called nanowires and nanoelectrodes), which are usually comprised of gold but can be other metals or conductive materials. For example, if especially sharp nanoelectrode tips are desired, a harder, more stable metal such as platinum or palladium can be deposited. Spacing between the nanoelectrode tips 13, 15 in the range of 1 nm to 10 μm produces good results.
In FIG. 1, a preselected metal 16 is deposited onto the tip of the cathode nanoelectrode 12. The metal 16 is usually platinum (Pt), but can be any metal that can be deposited electrolytically. The programmable, pulsable current source 18 has electrical leads 20, 22 to the respective nanoelectrodes 12, 14. A bypass circuit 24, which includes a bypass selector switch 26 and a variable resistor 28, is also shown.
The nanoelectrodes 12, 14 represent a subset of microscopic sized structures (nanostructures) that are suitable for use. Nanostructures acting as electrodes can be of various sizes and shapes. Spacing between the two nanostructures should not exceed 50 μm. Preferably, the spacing is 20 μm or less, more preferably 10 μm or less, and most preferably, 1 μm or less.
The programmable, pulsable current source 18 can be of any suitable construction. Keithley Model 220 programmable current source or the latest Keithley Model 2400 series of Source Meters (available from Keithley Instruments, Inc., 28775 Aurora Road, Cleveland, Ohio 44139, or on the Internet at www.keithley.com) are already capable of supplying a minimum of about 9400 electrons per pulse [500 fA×3 ms×electron/(1.60×10−19 C)]. This could translate to a deposition of 2350 platinum atoms per pulse based on the stoichiometry of the deposition reaction. If this amount of platinum is deposited on the end of a nanowire with a 10- by 10-nm cross section, 2350 platinum atoms per pulse can translate into about 1 nm of metal deposition (2.6 layers of platinum atoms) per pulse. The programmable, pulsable current source 18 should be capable of controlling the process so that nanometer metal deposition or depletion as precise as about 1500 metal atoms per pulse can be achieved. A preferable range is contemplated to be 1500 to 1014 atoms per pulse, although operation is possible well beyond this range.
The bypass circuit 24 is preferably added to fine-tune the electron flow for even more precise control of the deposition or depletion, i.e., the addition or removal of monolayers or submonolayers of atoms. The bypass circuit 24 is used to divert some of the electricity away from the nanoelectrodes 12, 14 in order to deposit (or deplete) fewer metal atoms per pulse. For example, when the impedance of the variable resistor 28 is adjusted to 50% of the impedance between the two nanoelectrodes 12, 14, two thirds of the 9400 electrons per pulse can be drained through the bypass circuit 24. In this case, the electrolytic metal deposition can be controlled to a step as precise as 780 platinum atoms (3130 electrons) per pulse. This translates to a deposition of 0.87 layer of platinum atoms 16 on a 10- by 10-nm surface at the tip of the cathode nanoelectrode 12. By allowing a greater portion of the current to flow through the bypass circuit 24, it is possible to control deposition of metal 16 atoms as precisely as 100 atoms per pulse. A preferable range for this extremely finely controlled deposition is contemplated to be 100–2500 atoms per pulse, although operation is possible well beyond this ultrafine deposition range.
The bypass circuit 24 can also protect the nanometer structure from electrostatic damage, especially when the structure is dry. For example, after desired programmable electrolytic metal deposition is achieved as illustrated in FIG. 1, the bypass circuit 24 should remain connected with the nanostructures 12 and 14 while the programmable pulsing current source can then be removed. As long as the bypass circuit remains connected with the nanostructures 12 and 14, any electrostatic charges that might be produced during wash and dry of the nanostructures will be able to flow through the bypass circuit 24. The bypass circuit 24 comprises the closed switch 26, the variable resistor 28, and wire leads that connect the switch 26 and the variable resistor 28 with the nanoelectrodes 12, 14. This prevents accumulation of electrostatic charges at any one of the electrodes against the other electrode from occurring, thus eliminating the possibility of electrostatic damage at the nanometer gap between the tips 13, 15 of the nanoelectrodes 12, 14.
A special nanostructural arrangement can be used to control the initiation point(s) of nanometer bonding. Special structural arrangements of the nanowire electrodes can now be made by various lithographic techniques to control the initiation point(s) of the electrolytic metal deposition. As shown in FIG. 2, multiple nanowire cathodes 12, 12′ should have respective tips 13, 13′ pointing to the respective tips 15, 15′ of nanoelectrode anode 14 so that the strongest electric field is therebetween. Spacing of the multiple nanowire cathodes 12, 12′ should be regulated to ensure deposition of metal 16, 16′ at the desired cathode location, because the electric field (E) is a vector that is strongly dependent on distance (r):E∝r−2.
In FIG. 3, electrolytic metal-dissolving reactions are applied to deplete metal, that is, to open nanometer gaps and control gap size. By conducting the reversal of the metal deposition reaction with sodium chloride solution instead of hexachloroplatinate as an electrolytic substrate, metallic platinum at the nanoelectrode anode tip 16 can be electrolytically depleted via dissolution in a controllable way according to the following reaction:Pt+6Cl−→[PtCl6]2−+4e−.This metal-dissolution reaction should also be able to control the gap size between the nanoelectrode tips 13, 15. The site and the extent of electrolytic metal depletion can also be controlled by proper selection of the desired polarity of the electric field and by use of a programmable current source with a bypass circuit, as described herein.
The salient features, as described hereinabove, may be applied in full, in part, or in any combination. Any number of nanostructures can be simultaneously bonded or dissolved on a particular substrate. The nanostructure to be metal-deposited does not have to be metal. Any conductive nanowires such as, for example, nanotubes (especially carbon nanotubes), can be connected because of their capability for nanometer electrolytic metal deposition. For metal depletion, the nonmetallic ions do not have to be Cl−. Any anions, such as F− and CN−, that can electrolytically dissolve metals (Pt, Pd, Au, etc.) may be used as alternative versions.
The above description is from our recently filed patent application entitled “Programmable Nanometer-Scale Electrolytic Metal Deposition and Depletion”; by James W. Lee and Elias Greenbaum; now U.S. Pat. No. 6,447,663; issued Sep. 10, 2002.